Chronic inflammatory pain resulting from arthritis, nerve injury and tumor growth is a serious public health issue. One of the major challenges in chronic inflammatory pain research is to develop new pharmacologic tre...Chronic inflammatory pain resulting from arthritis, nerve injury and tumor growth is a serious public health issue. One of the major challenges in chronic inflammatory pain research is to develop new pharmacologic treatments with long-term efficacy and few side effects. The mediators released from inflamed sites induce complex changes in peripheral and central processing by directly acting on transducer receptors located on primary sensory neurons to transmit pain signals or indirectly modulating pain signals by activating receptors coupled with G-proteins and second messengers. High local proton concentration(acidosis) is thought to be a decisive factor in inflammatory pain and other mediators such as prostaglandin, bradykinin, and serotonin enhance proton-induced pain. Proton-sensing ion channels [transient receptor potential V1(TRPV1) and the acid-sensing ion channel(ASIC) family] are major receptors for direct excitation of nociceptive sensory neurons in response to acidosis or inflammation.G-protein-coupled receptors activated by prostaglandin, bradykinin, serotonin, and proton modulate functions of TRPV1, ASICs or other ion channels, thus leading to inflammation- or acidosis-linked hyperalgesia. Although detailed mechanisms remain unsolved, clearly different types of pain or hyperalgesia could be due to complex interactions between a distinct subset of inflammatory mediator receptors expressed in a subset of nociceptors. This review describes new directions for the development of novel therapeutic treatments in pain.展开更多
Objective: To detect the expression changes of proton-sensing receptor G protein-coupled receptor 2A (G2A) and ovarian cancer G protein-coupled receptors 1 (OGR1) in human peripheral blood cells of patients with hypox...Objective: To detect the expression changes of proton-sensing receptor G protein-coupled receptor 2A (G2A) and ovarian cancer G protein-coupled receptors 1 (OGR1) in human peripheral blood cells of patients with hypoxia-induced pulmonary hypertension (HPH). Methods: Thirty-one patients with HPH were enrolled for IPH group, 16 males and 15 females, aged (65.19 ± 5.86) years;and 30 healthy people were enrolled for control group (NC group), 15 males and 15 females, aged (63.47 ± 6.16) years. The peripheral blood samples were collected and the mRNA expressions of G2A and OGR1 were determined by using real-time fluorescent quantitative PCR. The pulmonary arterial pressure (PAP) of HPH group was detected with echocardiography for the analysis of blood gas and pulmonary function testing. Human peripheral blood was collected to detect the mRNA levels of G2A, OGR1 and the serum levels of tumor necrosis factor-α (TNF-α). Results: PaCO2 was increased significantly in HPH group than that in NC group (p < .05). The percentage of forced expiratory volume in 1 s in predicted value (FEV1 pro%) and the ratio of FEV1/forced vital capacity (FVC) in HPH group were significant lower than those in NC group (p < .05). The expressions of peripheral blood G2A mRNA and TNF-α in HPH group were increased dramatically than those in NC group (p < .05). The expressions of OGR1 mRNA in peripheral blood had no difference between HPH group and NC group. The expressions of G2A mRNA and TNF-α in HPH group were positively related to pulmonary artery pressure significantly. Conclusions: The expression of proton-sensing receptor G2A and the level of TNF-α were increased in peripheral blood cells of patients with pulmonary hypertension. The expressions of TNF-α and G2A had positive correlations with pulmonary artery pressure.展开更多
G蛋白偶联受体家族卵巢癌G蛋白偶联受体1(ovarian cancer G protein-coupled receptor 1,OGR1)亚家族的OGR1、T细胞死亡偶联基因8(T-cell death associated gene 8,TDAG8)、G蛋白偶联受体4(G protein-coupled receptor 4,GPR4)及诱导细...G蛋白偶联受体家族卵巢癌G蛋白偶联受体1(ovarian cancer G protein-coupled receptor 1,OGR1)亚家族的OGR1、T细胞死亡偶联基因8(T-cell death associated gene 8,TDAG8)、G蛋白偶联受体4(G protein-coupled receptor 4,GPR4)及诱导细胞停滞于G2/M期的G蛋白偶联受体G2A(from G2 accumulation)4种受体是最新发现的一类质子感知受体.除了质子,体内又有它们各自特定的脂质分子配体活化这些受体来调节细胞机能.该类受体广泛分布于人的各种正常组织和肿瘤组织细胞中,在肿瘤的发生与转移、细胞骨架重组等生理病理过程中发挥双重作用.正常表达时它们有一定的抑制肿瘤作用,但这些受体的异常表达或过表达使某些组织和细胞恶性转化,导致肿瘤的发生.本文综述了在肿瘤组织的酸性微环境中,细胞表达的质子(pH)感知受体对肿瘤发生与肿瘤转移的调节作用及其相关的信号通路.展开更多
卵巢癌G蛋白偶联受体1 (ovarian cancer G protein-coupled receptor 1, OGR1)亚家族广泛分布于人体组织中,该受体具有质子敏感特性,可以通过受体组氨酸残基感知细胞外pH值变化,对人体细胞功能进行调节。质子感知受体不仅与肿瘤的发生...卵巢癌G蛋白偶联受体1 (ovarian cancer G protein-coupled receptor 1, OGR1)亚家族广泛分布于人体组织中,该受体具有质子敏感特性,可以通过受体组氨酸残基感知细胞外pH值变化,对人体细胞功能进行调节。质子感知受体不仅与肿瘤的发生、免疫系统、神经系统及血管系统等密切相关,还能调节成骨细胞骨形成和破骨细胞骨吸收来影响骨代谢。当骨形成和骨吸收动态平衡被打破以后,会导致骨量异常以及相关骨病的发生。本文就质子感知受体在骨代谢中的作用进行综述。展开更多
基金Supported by(In part)Intramural Funding from Academia Sinicaby grants from the National Science Council,Taiwan(NSC 102-2325-B-001-042 to Chen CCNSC 101-2321-B-008-001 to Sun WH)
文摘Chronic inflammatory pain resulting from arthritis, nerve injury and tumor growth is a serious public health issue. One of the major challenges in chronic inflammatory pain research is to develop new pharmacologic treatments with long-term efficacy and few side effects. The mediators released from inflamed sites induce complex changes in peripheral and central processing by directly acting on transducer receptors located on primary sensory neurons to transmit pain signals or indirectly modulating pain signals by activating receptors coupled with G-proteins and second messengers. High local proton concentration(acidosis) is thought to be a decisive factor in inflammatory pain and other mediators such as prostaglandin, bradykinin, and serotonin enhance proton-induced pain. Proton-sensing ion channels [transient receptor potential V1(TRPV1) and the acid-sensing ion channel(ASIC) family] are major receptors for direct excitation of nociceptive sensory neurons in response to acidosis or inflammation.G-protein-coupled receptors activated by prostaglandin, bradykinin, serotonin, and proton modulate functions of TRPV1, ASICs or other ion channels, thus leading to inflammation- or acidosis-linked hyperalgesia. Although detailed mechanisms remain unsolved, clearly different types of pain or hyperalgesia could be due to complex interactions between a distinct subset of inflammatory mediator receptors expressed in a subset of nociceptors. This review describes new directions for the development of novel therapeutic treatments in pain.
文摘Objective: To detect the expression changes of proton-sensing receptor G protein-coupled receptor 2A (G2A) and ovarian cancer G protein-coupled receptors 1 (OGR1) in human peripheral blood cells of patients with hypoxia-induced pulmonary hypertension (HPH). Methods: Thirty-one patients with HPH were enrolled for IPH group, 16 males and 15 females, aged (65.19 ± 5.86) years;and 30 healthy people were enrolled for control group (NC group), 15 males and 15 females, aged (63.47 ± 6.16) years. The peripheral blood samples were collected and the mRNA expressions of G2A and OGR1 were determined by using real-time fluorescent quantitative PCR. The pulmonary arterial pressure (PAP) of HPH group was detected with echocardiography for the analysis of blood gas and pulmonary function testing. Human peripheral blood was collected to detect the mRNA levels of G2A, OGR1 and the serum levels of tumor necrosis factor-α (TNF-α). Results: PaCO2 was increased significantly in HPH group than that in NC group (p < .05). The percentage of forced expiratory volume in 1 s in predicted value (FEV1 pro%) and the ratio of FEV1/forced vital capacity (FVC) in HPH group were significant lower than those in NC group (p < .05). The expressions of peripheral blood G2A mRNA and TNF-α in HPH group were increased dramatically than those in NC group (p < .05). The expressions of OGR1 mRNA in peripheral blood had no difference between HPH group and NC group. The expressions of G2A mRNA and TNF-α in HPH group were positively related to pulmonary artery pressure significantly. Conclusions: The expression of proton-sensing receptor G2A and the level of TNF-α were increased in peripheral blood cells of patients with pulmonary hypertension. The expressions of TNF-α and G2A had positive correlations with pulmonary artery pressure.
文摘G蛋白偶联受体家族卵巢癌G蛋白偶联受体1(ovarian cancer G protein-coupled receptor 1,OGR1)亚家族的OGR1、T细胞死亡偶联基因8(T-cell death associated gene 8,TDAG8)、G蛋白偶联受体4(G protein-coupled receptor 4,GPR4)及诱导细胞停滞于G2/M期的G蛋白偶联受体G2A(from G2 accumulation)4种受体是最新发现的一类质子感知受体.除了质子,体内又有它们各自特定的脂质分子配体活化这些受体来调节细胞机能.该类受体广泛分布于人的各种正常组织和肿瘤组织细胞中,在肿瘤的发生与转移、细胞骨架重组等生理病理过程中发挥双重作用.正常表达时它们有一定的抑制肿瘤作用,但这些受体的异常表达或过表达使某些组织和细胞恶性转化,导致肿瘤的发生.本文综述了在肿瘤组织的酸性微环境中,细胞表达的质子(pH)感知受体对肿瘤发生与肿瘤转移的调节作用及其相关的信号通路.
文摘卵巢癌G蛋白偶联受体1 (ovarian cancer G protein-coupled receptor 1, OGR1)亚家族广泛分布于人体组织中,该受体具有质子敏感特性,可以通过受体组氨酸残基感知细胞外pH值变化,对人体细胞功能进行调节。质子感知受体不仅与肿瘤的发生、免疫系统、神经系统及血管系统等密切相关,还能调节成骨细胞骨形成和破骨细胞骨吸收来影响骨代谢。当骨形成和骨吸收动态平衡被打破以后,会导致骨量异常以及相关骨病的发生。本文就质子感知受体在骨代谢中的作用进行综述。
